DOI QR코드

DOI QR Code

Expression of DNA Methylation Marker of Paired-Like Homeodomain Transcription Factor 2 and Growth Receptors in Invasive Ductal Carcinoma of the Breast

  • Rahman, Wan Faiziah Wan Abdul (Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus) ;
  • Fauzi, Mohd Hashairi (Department of Emergency Medicine, School of Medical Sciences, Universiti Sains Malaysia, Health Campus) ;
  • Jaafar, Hasnan (Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Health Campus)
  • 발행 : 2014.10.23

초록

Background: Paired-like homeodomain transcription factor 2 (PITX2) is another new marker in breast carcinoma since hypermethylation at P2 promoter of this gene was noted to be associated with poor prognosis. We investigated the expression of PITX2 protein using immunohistochemistry in invasive ductal carcinoma and its association with the established growth receptors such as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth receptor 2 (HER2). Methods: We conducted a cross sectional study using 100 samples of archived formalin-fixed paraffin embedded tissue blocks of invasive ductal carcinoma and stained them with immunohistochemistry for PITX2, ER, PR and HER2. All HER2 with scoring of 2+ were confirmed with chromogenic in-situ hybridization (CISH). Results: PITX2 protein was expressed in 53% of invasive ductal carcinoma and lack of PITX2 expression in 47%. Univariate analysis revealed a significant association between PITX2 expression with PR (p=0.001), ER (p=0.006), gland formation (p=0.044) and marginal association with molecular subtypes of breast carcinoma (p=0.051). Combined ER and PR expression with PITX2 was also significantly associated (p=0.003) especially in double positive cases. Multivariate analysis showed the most significant association between PITX2 and PR (RR 4.105, 95% CI 1.765-9.547, p=0.001). Conclusion: PITX2 is another potential prognostic marker in breast carcinoma adding significant information to established prognostic factors of ER and PR. The expression of PITX2 together with PR may carry a very good prognosis.

키워드

참고문헌

  1. Allred DC and Berardo HJ (1998). Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol, 11, 155-68.
  2. Ambroise M, Ghosh M, Mallikarjuna VS, Kurtian A (2011). Immunohistochemical profile of breast cancer patients at a tertiary care hospital in South India. Asian Pac J Cancer Prev, 12, 625-9.
  3. Das PM and Singal R (2004). DNA methylation and cancer. J Clin Oncol, 22, 4632-42. https://doi.org/10.1200/JCO.2004.07.151
  4. Ellis IO and Bartlett J (2004). Best Practice No. 176: updated recommendations for HER2 testing in the UK. J Clin Pathol, 57, 233-7. https://doi.org/10.1136/jcp.2003.007724
  5. Esteller M (2008). Epigenetics in cancer. N Engl J Med, 358, 1148-59. https://doi.org/10.1056/NEJMra072067
  6. Hasnan J, Suhaila A, Mogana DM, Fauziah MI (2012). Expression of Bax and Bcl-2 in tumour cells and blood vessels of breast cancer and their association with angiogenesis and hormonal receptors. Asian Pac J Cancer Prev, 13, 3857-62. https://doi.org/10.7314/APJCP.2012.13.8.3857
  7. Harbeck N, Nimmrich I, Hartmann A, et al (2008). Multicenter study using paraffin-embedded tumor tissue testing PITX2 DNA methylation as a marker for outcome prediction in tamoxifen-treated, node-negative breast cancer patients. J Clin Oncol, 26, 5036-42. https://doi.org/10.1200/JCO.2007.14.1697
  8. Harvey JM, Clark GM, Osborne CK & Allred DC (1999). Estrogen receptor status by immunohistochemistry is Superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer. J Clin Oncol, 17, 1474.
  9. Li CY, Zhang S, Zhang XB, et al (2013). Clinicopathological and prognostic characteristics of triple-negative breast cancer (TNBC) in Chinese patients: A retrospective study. Asian Pac J Cancer Prev, 14, 3779-84. https://doi.org/10.7314/APJCP.2013.14.6.3779
  10. Ma KK, Chau WW, Wong CHN, et al (2012). Triple negative status is a poor prognostic indicator in chinese women with breast cancer: a ten year review. Asian Pac J Cancer Prev, 13, 2109-14. https://doi.org/10.7314/APJCP.2012.13.5.2109
  11. Maier S, Nimmrich I, Koenig, T et al (2007). DNA-methylation of the homeodomain transcription factor PITX2 reliably predicts risk of distant disease recurrence in tamoxifentreated, node-negative breast cancer patients--Technical and clinical validation in a multi-centre setting in collaboration with the European Organisation for Research and Treatment of Cancer (EORTC) PathoBiology group. Eur J Cancer, 43, 1679-86. https://doi.org/10.1016/j.ejca.2007.04.025
  12. Nimmrich I, Sieuwerts AM, Meijer-van Gelder ME et al (2008). DNA hypermethylation of PITX2 is a marker of poor prognosis in untreated lymph node-negative hormone receptor-positive breast cancer patients. Breast Cancer Res Treat, 111, 429-37. https://doi.org/10.1007/s10549-007-9800-8
  13. Somali I, Ustaoglu BY, Tarhan MO, et al (2013). Clicopathologic and demographic evaluation of triple negative breast cancer patients among a turkish patient population: a single center experience. Asian Pac J Cancer Prev, 14, 6013-7 https://doi.org/10.7314/APJCP.2013.14.10.6013
  14. Tanner M, Gancberg D, Di Leo A, et al (2000). Chromogenic in situ hybridization: a practical alternative for fluorescence in situ hybridization: a practical alternative for fluorescence in situ hybridization to detect HER-2/neu oncogene amplification in archival breast cancer samples. Am J Pathol, 157, 1467-72. https://doi.org/10.1016/S0002-9440(10)64785-2
  15. Widschwendter M, Apostolidou S, Raum E, et al (2008). Epigenotyping in peripheral blood cell DNA and breast cancer risk: a proof of principle study. PLoS ONE, 3, 2656. https://doi.org/10.1371/journal.pone.0002656
  16. Yip CH, Taib NA & Mohamed I (2006). Epidemiology of breast cancer in Malaysia. Asian Pac J Cancer Prev, 7, 369-74.
  17. Zubeda S, Kaipa PR, Shaik NA, et al (2013). HER-2/neu status: A neglected marker of prognostication and management of breast cancer patients in India. Asian Pac J Cancer Prev, 14, 2231-5. https://doi.org/10.7314/APJCP.2013.14.4.2231

피인용 문헌

  1. Methylation in promoter regions of PITX2 and RASSF1A genes in association with clinicopathological features in breast cancer patients vol.37, pp.12, 2016, https://doi.org/10.1007/s13277-016-5324-3